A psoralen in which intracyclic oxygen atoms were replaced by sulfur (7H-thieno [3,2-g]--[benzothiopyran-7-one) [PSO(S-S)]) was recently synthesized and its photobiological properties were investigated. M13mp19 DNA photosensitization mediated by PSO(S-S) followed by transfection into competent E. coli gave rise to a very low phage progeny showing the high aptitude of this compound to modify DNA. In order to characterize the role of oxidative damages in the photosensitized reaction mediated by PSO( S-S), plasmid bearing the gene encoding the formamidopyrimidine DNA glycosylase (Fpg) under the control of the inducible lac Z promoter was transfected in E. coli. Overexpression of Fpg was induced by addition of isopropyl-β-D-thio-galactopyranoside (IPTG) to the cells and monitored by western blot analysis. Fpg overexpression did not influence the rate of M13mp19 DNA photoinactivation by PSO(S-S) neither the mutation frequency measured by the expression of β-galactosidase encoded by the lac Z gene beared by M13mp19. Analysis of the mutation patterns recorded with or without Fpg overexpression showed that several G to T transversions due to oxidative damages were repaired by Fpg. These data show that oxidative DNA damages generated during PSO(S-S) photosensitization have only limited biological implications measured in terms of DNA photoinactivation.
|Pages (de - à)||36-44|
|Nombre de pages||9|
|journal||Journal of Photochemistry and Photobiology B: Biology|
|Numéro de publication||1-2|
|Etat de la publication||Publié - 1 nov. 1997|